To establish the efficacy of targeted LV lead delivery in a sufficiently powered randomized, multicentre study. Efficacy is determined based on the distance of the LV-lead to the targeted cardiac segment, as determined pre-implantation by CARTBox.
ID
Source
Brief title
Condition
- Heart failures
- Cardiac therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the distance of the ultimateley selected electrode of a
quadripolar LV-lead to a pre-defined target. This will be determined on the
basis of a categorical variable and is based on fluroscopic images (LAO 40, RAO
30). As a consequence, lead location will be scored as residing within,
adjacent to or remote from a pre-defined target, as determined on a 32- and
16-segment *bulls eye" plot. In addition, LV leads position will be judged for
whether it is implanted in scar region (yes/no) and or implanted in a
dyssynchronous region (yes/no).
Secondary outcome
1. Short term efficacy after 6 months: 1) differences in echocardiographic LV
dimensions (end-systolic volume) and function (ejection fraction); 2)
proportion of pattients with a structural response, defined as a relative
reduction in LV end systolic volume >= 15%.
2. Short term functional response after 6 months: 1) differences in quality of
Life as determined by the Kansas City Cardiomyopathy Questionnaire; 2) New York
Heart Association (NYHA) classification and 3) EQ-5D.
3. Long term efficacy after one and two years: 1) all-cause mortality or heart
failure related hospitalisation; 2) clinical composite endpoint of death,
transplantation and LV assisting device; 3) functional response determined by a
Quality of Life questionnaire; 4) CRT response score.
4. Total cost of procedure and healthcare costs, using a Health Technology
Assessment (HTA) approach.
Background summary
Chronic heart failure is a major cause of morbidity and mortality in the
Netherlands. Heart failure accompanied by ventricular dyssynchrony, determined
by a wide QRS complex on het electrocardiogram (ECG), is a predictor for worse
prognosis. A wide QRS complex (>120ms) is present in about 25-50% of patients
with chronic heart failure. Cardiac resynchronization therapy (CRT) is an
important therapy for patients with dyssynchronized heart failure (ventricular
dyssynchrony). With a CRT device, a special pacemaker, the heart can be
electrically stimulated (via 3 pacemaker leads in the heart) in order to
achieve synchronized contraction once more.
Unfortunately up to 30-40% of patients do not benefit from CRT. Suboptimal
(left ventricular) lead positions are an imporant determinant for CRT
non-response. To place the CRT device the implanting cardiologist currently
uses fluoroscopic projections (2D X-ray images) of the heart. With this
approach, the optimal pacing site for the pacemaker leads, unfortunately, is
not visible. This is concerning, since multiple studies have addressed optimal
pacing sites for LV stimulation that result in improved response rates and
prognosis. Optimal pacing sites are charactarised by pacing in a targeted area
of latest mechanical contraction, while pacing in or near an area of myocardial
infarction reduces response to CRT. LV lead delivery to these optimal pacing
site however is challenging due to restrictions caused by the coronary venous
anatomy, areas with fibrosis (e.g. due to myocardial infarction) areas with
phrenic nerve stimulation and high pacing thresholds.
For improving CRT response, optimizing the final LV lead position is of major
importance. Unfortunately, the implanting physician currently has no
information on the optimal position. This is because, during CRT implantation,
fluoroscopic imaging provides no tissue characteristics. Consequently, and
despite already broad implementation of CRT during the past 20 years, LV-lead
placement is still most often solely based on empirical placement somewhere on
the LV lateral wall. Real-time visualisation of both infarct location and
latest contracting area during implantation could therefore improve final LV
lead position.
With a new techniqe we can merge MRI images of the heart (on which myocardial
scar tissue and mechanical contraction timing can be identified) with the
fluoroscopic 2D-projection made routinely during conventional CRT
implantations. Tthis technique potentially allows the physician to perform the
therapy much more accurate than before at the optimal pacing location in the
heart. Using this patient tailored approach we believe that response to CRT can
be augmented. Previous research already demonstrated that targeted therapy
(away from scar and toward the latest mechanical contraction) improves
patients' symptoms and prognosis.
We have recently demonstrated in a small pilot study that using the CARTBox
software, developed by CART-Tech B.V., the optimal location for LV lead
delivery can be visualized during CRT implantation (METC number 16/242). In the
ADVISE-CRT II study with 30 patients (METC number 19/443), the software behind
the technique has been improved. Moreover, 2D-imagefusion has been validated in
5 patients. To this end, no additional 3D rotational scan has to be performed
in the ADVISE III study. The ADVISE-III study will be a randomised controlled
trial with multiple centers (3 or more centers) in 130 patients. We therefore
hope to be able to draw more firm conclusions about the efficacy and feasibiliy
of real-time image-guided CRT implantations.
Study objective
To establish the efficacy of targeted LV lead delivery in a sufficiently
powered randomized, multicentre study. Efficacy is determined based on the
distance of the LV-lead to the targeted cardiac segment, as determined
pre-implantation by CARTBox.
Study design
The ADVISE-III trial is a multicentre, interventional, blinded, randomised
controlled trial. Patients will be stratified according to ethology of HF, to
assure equal distribution of patients with ischemic cardiomyopathy (ICM) and
non-ICM patients in both groups. We will use the CARTBox software during CRT
implantation for targeting the LV-lead implantation towards predefined optimal
pacing sites. Both the patient and the sonographer will be blinded from
treatment outcome.
Intervention
CRT procedure (conventional), but carried out under guidance of CARTBox
software (new) in the interventiongroup.
Study burden and risks
All patients will undergo an MRI scan. In rare cases (<1/1000) an allergic
reaction can occur, such as an itch, nausea or small bumps on the skin. In the
vast majority of cases these symptoms pass quickly. In extremely rare cases
acute allergic reactions can occur, usually in subjects with known contrast
allergies. Therefore, these subjects are excluded from participation in this
study. Recently nephrogenic systemic fibrosis (NFS) has been linked to
administration of gadolinium-based contrast agents in subjects with renal
failure. Therefore, subjects with renal failure are excluded from an MRI scan.
No cases of NFS have been documented in patients without renal failure.
The benefit of the Cardiac MRI is the knowledge of scar tissue, detailed
description of LV function, and visualization of the LV region with late
contraction where the LV lead has to be placed. For the patient, the additional
burden of the MRI is the extra visit to the hospital and claustrophobic
patients may not be able to undergo the assessment. The risk and/or
complications of the CRT implantation itself are not additional to the study,
as the CRT implantation with a quadripolar lead is a standard procedure in the
UMC Utrecht. Cardiac MRI scan will be performed before CRT implantation.
During implantation, a 2D registration method for fusing MRI with fluoroscopy
wll be used. Therefore, since no additional 3D rotational scan is made, total
radiation burden is similar to conventional procedures.
The study can increase the response of patients to CRT. By fusing MRI images
with fluoroscopy during LV lead positioning, the implanting physician can
choose the most optimal position (out of scar and towards delayed contraction)
for implanting the CRT device. A lead position away from the infarct area, and
closest to or in the latest activated area will improve LV pump function. An
improved response to CRT can improve quality of life and prognosis of heart
failure patients. Especially patients with myocardial infarction and/or
coronary artery stenosis (ischemic cardiomyopathy), since these patients are
more often non-responders to CRT. The study may also improve the procedure
itself. With increased knowledge of an optimal lead position during
implantation, future procedures can be conducted more easily. The implanting
physician can choose a target vessel for optimal lead position. It can
therefore shorten the procedure and prevent potential complications of
prolonged procedures.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
An indication for cardiac resynchronization therapy according to the current
international evidence based guidelines for CRT (the 2016 European Society of
Cardiology Guidelines for Acute and Chronic Heart Failure:
- Chronic heart failure;
- New York Heart Association functional class II, III, IV (ambulatory);
- QRS duration >=130ms;
- Optimal pharmacological therapy;
- Left ventricular ejection fraction <=35%;
- Either a QRS duration >=130ms with left-bundle branch block OR a QRS duration
>=150ms without left-bundle branch block.
Exclusion criteria
Contraindications for implantation of a CRT device;
- Age <18 years or incapacitated adult;
- Pregnancy; if there is anamnestic doubt regarding postmenopausal state (<1
year since last menstruation), a urine hCG test (Alere) will be performed.
- Lactation;
- Subjects with impaired renal function (severe renal insufficiency, GFR < 30
ml/min/1.73m2);
- Atrial fibrillation or atrial fibrillation during MRI
- Documented allergic reaction to gadolinium;
- Impossibility to undergo a MRI scan (determined by using the standard
contraindications for MR imaging as used for clinical purposes).
- Participation in another clinical study that prohibits or influences any
procedures other than standard.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL73416.041.20 |
| OMON | NL-OMON29327 |